Food allergy is a serious health problem with increasing incidence. Peanut is one of the most life threatening allergenic foods. In contrast to allergic disease due to inhalant allergens, there are no effective treatments other than strict avoidance and rapid intervention with epinephrine when reactions do occur. Peanut-induced allergic reactions are mediated by antigen-specific IgE bound to the high-affinity receptor for IgE (Fc RI) on mast cells and basophils. Mast cells and basophils play critical roles in allergic inflammation. The long-term objective of this proposal is to develop a new form of peanut-human fusion protein for treatment of peanut- induced allergy. Here we hypothesize that peanut allergen-Fc fusion protein may block peanut-induced allergic reaction and serve as allergen immunotherapy to induce a protective immune response. To achieve this goal, we will test the ability of peanut-human fusion protein to acutely inhibit peanut-induced allergic response in a peanut-induced allergic mouse model that consists of both early and late phase responses to oral challenge with peanut. To test a long term effect induced by the allergen-gamma fusion protein, we plan to develop a peanut allergen-mouse Fc 2a fusion protein. We will explore the mechanism of allergen-gamma fusion protein-induced immune responses in vivo. We will determine whether the allergen-mouse Fc protein induces a protective immune response in mice. We will also treat mice with allergen-gamma fusion protein and determine if mice treated with allergen-gamma fusion protein will be protected from challenge with complete peanut extract. If these experiments work as projected, this approach may lead the way to the first effective therapy for humans with severe allergy to peanut. This proposal is directed toward developing a therapeutic strategy for peanut allergy by using a recombinant peanut-human fusion protein. This molecule will be allergen specific and may provide a new platform for allergen immunotherapy of food allergy.